This is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy of controlled-release (CR) formulation of paroxetine orally administered to patients with major depressive disorder (MDD) at a dose level in the range of 25 - 50 mg/day (initial dose level, 12.5 or 25 mg/day) once daily after evening meal for 8 weeks based on the decrease in HAM-D (Hamilton Depression Rating Scale) total score, to evaluate the safety based on adverse events, laboratory data and vital signs, and to describe the efficacy and safety of immediate release (IR) formulation of paroxetine.

The HAM-D measures the severity of depressive symptoms in participants with major depressive disorder (MDD). It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Mean change from baseline was calculated as the value at Week 8 minus the Baseline value.

The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Mean change from baseline was calculated as the value at each time point minus the Baseline value.

The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is a sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Responders are defined as participants with a 50 percent or greater reduction from baseline in the HAM-D total score.

The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Remitters are defined as participants with a HAM-D total score of 7 or less.

The 7-point CGI-SI scale assesses the clinician's impression of the participant's current illness state. Scores on the CGI-SI range from 1 = not ill at all to 7 = among the most extremely ill. Mean change from baseline was calculated as the value at each time point minus the baseline value.

Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 [ Time Frame: Weeks 4 and 8 ] [ Designated as safety issue: No ]

The 7-point CGI-GI assesses the participant's improvement or worsening from baseline. Scores on the CGI-GI range from 1 = very much improved to 7 = very much worse. Responders are defined as participants with a score of 1 or 2 = much improved.

Immediate-release (IR) of paroxetine 10 to 40mg/day as a reference arm

Drug: paroxetine IR 10mg tablet

1 or 2 tablets once a day

Drug: paroxetine IR 20mg tablet

1 tablet once a day

Drug: matched placebo to paroxetine IR 10mg or 20mg

1 or 2 tablets once a day

Drug: matched placebo to paroxetine CR 12.5mg or 25mg

1 or 2 tablets once a day

Placebo Comparator: placebo group

matched placebo to both paroxetine CR and paroxetine IR

Drug: matched placebo to paroxetine IR 10mg or 20mg

1 or 2 tablets once a day

Drug: matched placebo to paroxetine CR 12.5mg or 25mg

1 or 2 tablets once a day

Eligibility

Ages Eligible for Study:

20 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

<at the start of placebo run-in phase> Only the patients who meet all of the following conditions at Week -1 (at the start of placebo run-in phase) will be enrolled in this study. The hospitalization status will be no object. and Gender: No object.

Target disease: Patients diagnosed as having one of the following depressive disorders based on DSM-IV-TR classification in conjunction with M.I.N.I. (The Mini International Neuropsychiatric Interview, Japanese version 5.0.0. [2003]) and showing currently a symptom of depression or depressed sate

Major depressive disorder, single episode (296.2) (excluding those accompanied by comorbid psychiatric disorders)

Consent: Patients from whom written consent to participate in this study can be obtained

Gender:

Female patients of childbearing potential can be enrolled. But, such patients who can be enrolled are limited to only those who are negative in the pregnancy test performed at the start of the placebo run-in phase and who agree to receive a pregnancy test at the time point defined in the study period and surely perform any of the contraceptive methods.

Male subjects must abstain from (or use a condom during) sexual intercourse with a pregnant or lactating female. Male subjects must abstain from or use a condom plus spermicidal agent (foam/gel/film/cream/suppository) during sexual intercourse with a female of child-bearing potential.

Patients whose HAM-D (17 items) total score is >= 20 points

Patients whose duration of current episode at least 12 weeks but no longer than 24 months

QTc<450 millisecond (msec) or <480 msec for patients with Bundle Branch Block - values based on either single ECG values or triplicate ECG averaged QTc values obtained over a brief recording period.

For the purposes of these criteria, QTc B (Bazett's correction) is defined as (QT interval [msec]) /(square root of RR interval [seconds])

<at the start of treatment phase> Only the patients who meet all of the following conditions at Week -1 (at the start of the placebo run-in phase) and Week 0 (at the start of treatment phase) can be shifted to the treatment phase.

Patients whose HAM-D (17 items) total score is >=20 points

Patients whose score of "depressed mood" (HAM-D Item 1) is >=2 points

Exclusion Criteria:

<at the start of placebo run-in phase> The patients who are meeting any of the following conditions at Week -1 (at the start of placebo run-in phase) must not be enrolled in this study.

Patients with a current DSM-IV-TR Axis II diagnosis that suggested non-responsiveness to pharmacotherapy or non- compliance with the protocol (e.g., antisocial or borderline personality disorder)

Patients with a history or complication of another (non-MDD) mental disorder (schizophrenia, etc.)

Patients with a history or complication of manic episodes

Patients diagnosed as having an attentional deficit disorder or hyperactivity disorder

Patients diagnosed as having a pervasive development disorder or mental retardation

Patients diagnosed as abusing or dependent on alcohol or drug within one year before the Week -1 visit

Patients who have undergone electroconvulsive therapy within one year before the Week -1 visit for the treatment of the current episode

Patients who have a history of treatment with depot neuroleptics

Patients with a history of serotonin syndrome or neuroleptic malignant syndrome

Patients with a >= 3-point score of "suicide" (HAM-D Item 3) or patients whose Columbia Suicide Severity Rating Scale (C-SSRS) assessment suggests that they are or have been at significant risk for harming themselves or have actually harmed themselves, or who, in the opinion of the investigator (subinvestigator), are at significant risk for harming self or others.

Patients with a history of suicide attempt, self-injurious action (excluding action with no intention of suicide) or overdosage (excluding apparently accidental overdosage)

Patients who have taken another investigational product or a drug used in a post-marketing clinical study within 12 weeks before the Week -1 visit

Patients with glaucoma

Patients with a convulsive disorder such as epilepsy or a history of it

Patients using a drug increasing an onset risk of bleeding, patients with a bleeding tendency or bleeding diathesis

Pregnant, lactating or possibly pregnant female patients, and female patients wishing to be pregnant during the study period

Patients who have previously been unresponsive to paroxetine therapy (e.g. >4wks unresponsive to paroxetine for depression).

Patients with a history of having discontinued treatment due to an adverse event caused by paroxetine

Patients with a history of hypersensitivity to paroxetine.

Patients judged ineligible to participate in this study by the investigator or subinvestigator

Exclusion criteria < at the start of treatment phase> The patients who are meeting any of the following conditions at Week 0 (at the start of treatment phase) must not be allowed to the treatment phase.

Patients with a 3 or more-point score of "suicide" (HAM-D Item 3) or with a strong suicidal tendency by C-SSRS and investigator clinical judgement.

Patients whose HAM-D (17 items) total score at the Week 0 visit has changed ±25 %, or exceeding the range of ±25 % of the score at the Week -1 visit

Patients whose Drug 1 (run-in placebo) compliance rate in the period from Week -1 to Week 0 has been < 80 %

Patients judged ineligible as the study subjects by the investigator or subinvestigator

Contacts and Locations

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For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866294